
Novel Chimerical Endolysins with Broad Antimicrobial Activity Against Methicillin-ResistantStaphylococcus aureus
Author(s) -
Sofia Fernandes,
Daniela Proença,
Cátia Cantante,
Filipa Antunes Silva,
Clara Leandro,
Sara Lourenço,
Catarina Milheiriço,
Hermı́nia de Lencastre,
Patrícia CavacoSilva,
Madalena Pimentel,
Carlos São-José
Publication year - 2012
Publication title -
microbial drug resistance
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 70
eISSN - 1931-8448
pISSN - 1076-6294
DOI - 10.1089/mdr.2012.0025
Subject(s) - lysin , lytic cycle , microbiology and biotechnology , bacteriophage , biology , staphylococcus aureus , antimicrobial , peptidoglycan , bacteria , escherichia coli , virology , genetics , virus , gene
Due to their bacterial lytic action, bacteriophage endolysins have recently gained great attention as a potential alternative to antibiotics in the combat of Gram-positive pathogenic bacteria, particularly those displaying multidrug resistance. However, large-scale production and purification of endolysins is frequently impaired due to their low solubility. In addition, a large number of endolysins appear to exhibit reduced lytic efficacy when compared with their action during phage infection. Here, we took advantage of the high solubility of two recently characterized enterococcal endolysins to construct chimeras targeting Staphylococcus aureus. The putative cell wall binding domain of these endolysins was substituted by that of a staphylococcal endolysin that showed poor solubility. Under appropriate conditions the resulting chimeras presented the high solubility of the parental enterococcal endolysins. In addition, they proved to be broadly active against a collection of the most relevant methicillin-resistant S. aureus epidemic clones and against other Gram-positive pathogens. Thus, fusion of endolysin domains of heterologous origin seems to be a suitable approach to design new potent endolysins with changed and/or extended lytic spectrum that are amenable to large-scale production.